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Zebrafish as a Model for Epilepsy-Induced Cognitive Dysfunction: A Pharmacological, Biochemical and Behavioral Approach

机译:斑马鱼作为癫痫诱发的认知功能障碍的模型:药理,生化和行为方法。

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Epilepsy is a neuronal disorder allied with distinct neurological and behavioral alterations characterized by recurrent spontaneous epileptic seizures. Impairment of the cognitive performances such as learning and memory is frequently observed in epileptic patients. AEDs are efficient to the majority of patients. However, 30% of this population seems to be refractory to the drug treatment. These patients are not seizure-free and frequently they show impaired cognitive functions. Unfortunately, as a side effect, some AEDs could contribute to such impairment. The major problem associated with conducting studies on epilepsy-related cognitive function is the lack of easy, rapid, specific and sensitive in-vivo testing models. However, by using a number of different techniques and parameters in the zebrafish, we can incorporate the unique feature of specific disorder to study the molecular and behavior basis of this disease. In the view of current literature, the goal of the study was to develop a zebrafish model of epilepsy induced cognitive dysfunction. In this study, the effect of AEDs on locomotor activity and seizure-like behavior was tested against the pentylenetetrazole (PTZ) induced seizures in zebrafish and epilepsy associated cognitive dysfunction was determined using T-maze test followed by neurotransmitter estimation and gene expression analysis. It was observed that all the AEDs significantly reversed PTZ induced seizure in zebrafish, but had a negative impact on cognitive functions of zebrafish. AEDs were found to modulate neurotransmitter levels, especially GABA, glutamate, and acetylcholine and gene expression in the drug treated zebrafish brains. Therefore, combination of behavioral, neurochemical and genenetic information, makes this model a useful tool for future research and discovery of newer and safer AEDs.
机译:癫痫病是一种神经元疾病,伴有明显的神经系统和行为改变,特征是反复发作的自发性癫痫发作。在癫痫患者中经常观察到诸如学习和记忆之类的认知能力受损。 AED对大多数患者有效。但是,这一人群中有30%似乎对药物治疗无效。这些患者并非没有癫痫发作,并且常常表现出认知功能受损。不幸的是,作为副作用,某些AED可能导致这种损害。与癫痫相关的认知功能进行研究有关的主要问题是缺乏简单,快速,特异和敏感的体内测试模型。但是,通过在斑马鱼中使用多种不同的技术和参数,我们可以结合特定疾病的独特特征来研究这种疾病的分子和行为基础。根据目前的文献,该研究的目的是建立一种由癫痫引起的认知功能障碍的斑马鱼模型。在这项研究中,针对戊烯四唑(PTZ)诱发的斑马鱼癫痫发作,测试了AED对运动活动和癫痫样行为的影响,并使用T-迷宫测试,神经递质估计和基因表达分析确定了癫痫相关的认知功能障碍。观察到所有的AEDs都能明显逆转PTZ引起的斑马鱼癫痫发作,但对斑马鱼的认知功能有负面影响。发现AED可以调节药物治疗的斑马鱼大脑中的神经递质水平,尤其是GABA,谷氨酸和乙酰胆碱以及基因表达。因此,行为,神经化学和遗传信息的结合,使该模型成为未来研究和发现更新和更安全的AED的有用工具。

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